An immunochemical approach aiming at increasing therapeutic index of anthracycline antibiotics (adriamycin, duanomycin) is a main thrust of this proposal. This will be achieved by means of i) selective targeting of drug to tumor cell utilizing distinct type of antibodies as carrier covalently or noncovalently and ii) decreasing in the cardiotoxicity of adriamycin by the conjugate formation with antibodies. Monoclonal antibodies capable of binding to either common (cross-reacting) or to specific antigenic determinants expressed on the chemically transformed cells are produced by the lymphocyte hybridoma technique. After the isolation of monoclonal antibodies via an immunosorbent, they are covalently linked to adriamycin or daunomycin by various coupling reagents including meta-maleimidobenzoyl N-hydroxysuccinimide ester, glutaraldehyde, cyanogen bromide, dextran and periodate-borohydride. The drug and antibody activities in the conjugates will be tested in vitro by the inhibition of H-thymidine incororated into DNA and the membrane immunofluorescence on various chemically transformed cells bearing either common and/or specific antigenic determinants. The therapeutic value of these adriamycin-antibodies conjugates as well as noncovalent mixture of drug and antibodies will be assessed in syngeneic mice bearing several transformed clones. The cardiotoxicity of conjugates will be evaluated both by in vitro method using cultured cardiac cells and by in vivo method using rabbit. The result of these studies on preclinical models will reveal i) the nature of surface antigens on malignantly transformed cells exploitable for therapy, ii) the role of antibodies on monitoring therapeutic index and cardiotoxicity of anthracycline antibiotics, and iii) the susceptibility of different tumor clones in response to the treatment by adriamycin antibodies conjugates. These informations should be useful in understanding the potential application of immunochemotherapeutic principles for the treatment of human cancer.